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Narcolepsy

Narcolepsy is defined as a disorder of rapid onset of rapid eye movement (REM) sleep. Narcolepsy is characterised by frequent and uncontrollable sleep attacks, excessive daytime sleepiness, and sleep fragmentation in a patient. These symptoms can be associated with sleep paralysis and hallucinations. Narcolepsy can also be defined as a disorder that affects the brain's ability to control wakefulness and sleep. Incidence of narcolepsy is one in 2000 Americans. Males are more affected by narcolepsy than the female gender. Family history is responsible for about 10% of individuals who experience narcolepsy. Narcolepsy is common in all age groups. However, the initial signs of narcolepsy appear in teenagers. Narcolepsy is often underdiagnosed as it causes symptoms of sleep disorders, depression, and such, which are also associated with other illnesses. Thus, narcolepsy may go untreated for many years.

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Types

Narcolepsy can be divided into the following two types:


  • Narcolepsy type 1 (formerly narcolepsy with cataplexy): Patients suffering from type 1 narcolepsy experience excessive daytime sleepiness with low hypocretin levels ( A chemical in the brain).

  • Type 2 narcolepsy (formerly narcolepsy without cataplexy): Patients suffering from type 2 narcolepsy experience excessive sleepiness during the daytime but do not have the symptoms of cataplexy. They have normal levels of the brain's chemical hypocretin.

Symptoms

The symptoms of narcolepsy include:


  • Excessive daytime sleepiness: The patients who develop narcolepsy have this symptom that interferes with the individual's social activities, school and home life. However, small naps during the daytime may help the individual feel alert and rested, but the tiredness will return after an hour or two. Patients experiencing excessive daytime sleepiness have been reported with loss of energy and concentration, depressed mood, memory lapses or extreme exhaustion.

  • Disturbed night-time sleep: The patient with narcolepsy experiences disturbance in night sleep by frequent awakenings.

  • Hallucinations: Individuals experience vivid and frightening delusions before falling asleep (hypnagogic hallucinations) or after waking up (hypnopompic hallucinations). These hallucinations are primarily visual, but sometimes you can also smell, taste or hear things.

  • Sleep paralysis: Patients with narcolepsy can experience sleep paralysis due to which an individual experiences an inability to move or speak before falling asleep or after waking up. Episodes of sleep paralysis go away after a few seconds to a few minutes.

  • Automatic behaviour: Automatic behaviour such as falling asleep for several seconds while performing a routine task such as talking, eating, driving or writing without any alertness.

  • Cataplexy: Patients with narcolepsy can experience a sudden loss of strength or muscle tone due to emotions such as fear, stress, anger, surprise or laughter. These attacks range from quick buckling of knees or dropping of the eyelids to total body paralysis and collapse. Cataplexy can last for a few seconds to several minutes. And the individual will remain fully conscious during a cataplexy attack. The frequency of these attacks can be several times a day, but no severe damage from these attacks is noted.

Causes And Risk Factors

Causes


The causes of narcolepsy can be associated with the loss of a hypocretin chemical signal in the brain. Hypocretin is vital in the regulation of the sleep-wake cycle and the rapid eye movement sleep state. The absence of hypocretin causes excessive sleepiness during the daytime, and some of the features of rapid eye movement sleep such as "dreaming sleep".

Some of the other possible causes of narcolepsy are as follows:

  • Family history is a significant factor that can cause narcolepsy.

  • Infections related to the brain can also cause narcolepsy.

  • An autoimmune disorder attacks the brain cells, which produce hypocretin, resulting in a shortage of the chemical in the brain; this can lead to narcolepsy.

  • This tumour, trauma or disease can cause brain injury, especially to that part of the brain that controls rapid eye movement, sleep and wakefulness.

  • Environmental reasons such as heavy metals in drinking water, passive smoking and exposure to pesticides can lead to narcolepsy.


Risk Factors


A family history of narcolepsy is one of the risk factors for developing this condition. An autoimmune disorder, presence of tumour or Infections can be possible risk factors for developing narcolepsy.

Prevention

Prevention of narcolepsy is not possible, but certain preventive measures such as avoiding exposure to toxins or infections, and regulating the sleep and wake cycles are beneficial.

Diagnosis

Narcolepsy can be diagnosed by a physical examination accompanied by a diagnostic workup. In addition, an individual may be asked to maintain a sleep diary in which he might note the frequency of falling asleep, staying asleep, the duration of sleep, and the feeling of waking up.

Two sleep studies that help determine the diagnosis of narcolepsy are:


  • Polysomnogram (PSG): This is an overnight test that measures multiple parameters such as heart rate, breathing rate, oxygen level, leg movements and eye movements while you sleep. Polysomnogram measures the ‘fall-asleep’ frequency, the frequency during which REM sleep is disturbed. This study will also help rule out other causes of this condition. Patients with narcolepsy usually depict abnormal sleep patterns with more frequent awakenings.

  • The multiple sleep latency test (MSLT): Multiple sleep latency tests measure how quickly an individual enters into a rapid eye movement sleep. This test is performed during the daytime after the PSG test. During this test, an individual has to take five short naps scheduled 2 hours apart.

Treatment

Treatment of narcolepsy comprises medications along with lifestyle changes.

Behaviour Modification: Behaviour modification can be effective with 15 to 20-minute long naps strategically scheduled throughout the day and maintaining an adequate night-time sleep schedule. The first-line pharmacologic treatment for excessive daytime sleepiness is modafinil (twice-daily dosing) or armodafinil (once-daily dosing). The second-line treatment would be amphetamines. The first-line treatment for cataplexy is sodium oxybate (Xyrem), a form of gamma-hydroxybutyrate, or GHB. The medication is taken while in bed due to the short onset of sleepiness, usually 5 to 15 minutes. A second dose is given 2.5 to 4 hours later. Xyrem is a restricted medication distributed from a central pharmacy. While there are concerns about abuse, dependence, and illegal use of Xyrem, post-market research has not proven these concerns to be valid. Tricyclic antidepressants (protriptyline, clomipramine) and SNRI/SSRIs (venlafaxine, fluoxetine) have also been used with some success in treating cataplexy. [13][14] Nonpharmacological treatments

Besides encouraging good sleep hygiene, the following measures are important:


  • Provide emotional support

  • Provide mental health counselling

  • Assist with disability forms and obtaining medications

  • Educate about the harms of alcohol and illicit drug use


Drug therapy: While several CNS stimulants are used to treat narcolepsy, none is 100% effective in all patients. Methylphenidate does improve sleep, but it also has undesirable side effects like anxiety, headache, and irritability. Modafinil does induce wakefulness, but its safety in children has not yet been established. Armodafinil is also effective for narcolepsy and has the same side effect profile as methylphenidate. Sodium oxybate is the only FDA-approved treatment for cataplexy, but it should not be combined with other CNS depressants or alcohol. Just recently, the FDA approved pitolisant (a histamine H3 receptor antagonist) for narcolepsy. Early studies indicate that it can improve sleep.

Currently, no medication has been approved by the FDA for use in children.

Lifestyle Modifications

Lifestyle modifications play a very vital role in the management of narcolepsy.


  • Keep your bedroom dark and quiet while sleeping.

  • Follow regular sleep and wake schedule by going to bed and waking up at the same time. Avoid staying up late at night on weekends which can disturb your sleep cycle.

  • Avoid smoking in the evening or before going to sleep.

  • Regular exercise for at least half an hour a day is effective; however, do not exercise 3 hours before bedtime.

  • Avoid caffeine and alcohol-containing products several hours before bedtime.

  • Avoid heavy meals and consume a lot of liquids before bedtime.

  • Take short naps of 20 to 30 minutes when you feel sleepy.

  • Relaxation before falling asleep by taking a warm bath, performing some gentle yoga, and meditating on soft music can help you to fall asleep.

Prognosis And Complications

Prognosis


The prognosis of narcolepsy may worsen or move to cataplexy with a changed diagnosis of Narcolepsy type 1. The prognosis of narcolepsy in children is poor with decreased performance in school and social interactions.

Complications


Complications of Narcolepsy are associated with mood disorders like depression and anxiety.

Alternative Treatments

No alternative treatments were found.

References.

1. Stat Pearls. Narcolepsy [Updated on December 3, 2020] Available at https://www.ncbi.nlm.nih.gov/books/NBK459236/.

2. Cleveland Clinic. Narcolepsy [Internet] Available at https://my.clevelandclinic.org/health/diseases/12147-narcolepsy.

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